This invention is in the field of neuropharmacology, and relates to methods of treating patients suffering from emotional problems that occur in relation to neurodegenerative diseases or to brain damage such as caused by stroke or head injury.
The phrase "emotional lability" is used by psychiatrists and neurologists to refer to a set of symptoms that are often observed in patients who have suffered a brain insult such as a head injury, stroke, brain tumor, or encephalitis, or who are suffering from a progressive neurodegenerative disease such as amyotrophic lateral sclerosis (ALS, also called motor neuron disease or Lou Gehrig's disease), Parkinson's disease, Alzheimer's disease, or multiple sclerosis. In the great majority of such cases, emotional lability occurs in patients who have bilateral damage (i.e., damage which affects both hemispheres of the brain) involving subcortical forebrain structures.
Emotional lability, which is distinct from clinical forms of reactive or endogenous depression, is characterized by intermittent spasmodic outbursts of emotion (usually manifested as intense or even explosive crying or laughing) at inappropriate times or in the absence of any particular provocation. The feelings that accompany emotional lability are often described in words such as "disconnectedness," since patients are fully aware that an outburst is not appropriate in a particular situation, but they do not have control over their emotional displays. Emotional lability is also described by some as "emotional incontinence," which draws an analogy between someone who is unable to control emotional outbursts, and someone who is unable to control their bladder or bowels.
Emotional lability becomes a clinical problem when the inability to control emotional outbursts interferes in a substantial way with the ability to engage in family, personal, or business affairs. For example, a businessman suffering from early-stage ALS or Parkinson's disease might become unable to sit through business meetings, or a patient might become unable to go out in public, such as to a restaurant or movie, due to transient but intense inability to keep from crying or laughing at inappropriate times in front of other people. These symptoms can occur even though the patient still has more than enough energy and stamina to do the physical tasks necessary to interact with other people. Such outbursts, along with the feelings of annoyance, inadequacy, and confusion that they usually generate and the visible effects they have on other people, can severely aggravate the other symptoms of the disease; they lead to feelings of ostracism, alienation, and isolation, and they can render it very difficult for friends and family members to provide tolerant and caring emotional support for the patient. Accordingly, emotional lability needs to be regarded as a distinct symptom that causes considerable suffering, and an effective method of treating it would be very helpful to sufferers and their families.
The best previously known therapies for treating emotional lability involve the drugs amitriptyline, amantadine, and levodopa. Although reports such as Udaka et al 1984 and Schiffer et al 1985 (complete citations are provided below, before the claims) indicate that these compounds may be effective in helping reduce pathological displays of emotion in some patients, they make it clear that none of these prior art drugs are effective in all patients, and even in patients who receive some benefit, the effect usually stops far short of an effective cure. A common practice for many clinical neurologists is to prescribe amitriptyline and amantadine, one at a time, in the hope that one of them might be able to provide any level of improvement in the patient's condition. However, all both fall short of offering an effective cure. In addition, levodopa is not satisfactory, since it has other effects and is a relatively powerful drug.
Accordingly, there remains a need for additional or improved forms of treatment for emotional lability. Such a treatment should provide, at a minimum, at least some degree of improvement compared to other known drugs, in at least some patients.
In fact, the treatment described herein has provided a truly remarkable and outstanding level of improvement in a number of the patients tested to date. This improvement was so beneficial and so clear that it quickly became apparent and came to the forefront as a primary effect of the treatment, even though the treatment was being evaluated for an entirely different purpose.
One object of this invention is to provide a method for treating emotional lability in at least some patients suffering from neurologic impairment, such as a progressive neurologic disease.
Another object of this invention is to disclose that dextromethorphan, which is known to selectively block activity at the NMDA class of glutamate receptors in the central nervous system (CNS) and which has some utility in protecting CNS neurons against death or damage due to certain toxic processes, has been discovered to have a separate and distinct beneficial effect: it is highly effective in reducing the external symptoms and the internal feelings of emotional lability in at least some patients who, prior to treatment, were suffering from an inability to control inappropriate emotional outbursts.